tbuckley/cabot-search huggingface dataset:
Spatial Analysis of Access to Psychiatrists for US Military Personnel and Their Families
Authors: Marigee Bacolod, Jennifer Heissel, Yu-Chu Shen
Journal: JAMA Network Open (2023)

Importance Military service members and their families have greater mental health care needs compared with their civilian counterparts. Some communities have inadequate access to psychiatrists for this population. Objectives To identify geographic variations in the availability of military and civilian psychiatrists within a 30-minute driving time of TRICARE (the US military’s health care program) beneficiaries’ communities and compare the likelihood of living in areas with inadequate access to psychiatrists for historically underserved and other communities. Design, Setting, and Participants This retrospective cohort study of all zip code communities in the continental US, Hawaii, and Alaska with at least one TRICARE beneficiary between January 1, 2016, and September 30, 2020, combines data from the Defense Health Agency, the National Plan and Provider Enumeration System, and the US Census to estimate a logistic regression to compare differences between communities with and without a psychiatrist shortage. Data were analyzed from September 2021 to November 2022. Main Outcomes and Measures A community’s likelihood of having a shortage of military and civilian psychiatrists within a 30-minute driving time and a community’s likelihood of having no psychiatrists. Odds ratios were calculated to estimate likelihood of the outcomes. Results This study includes 39 487 unique communities where 13% of the population is Black and 14% of the population is Hispanic. During the study period, 35% of TRICARE beneficiaries lived in communities with a shortage of both military and civilian psychiatrists, and 6% lived in communities with no access to military or civilian psychiatrists. Low-income communities with high income inequality were 1.64 (95% CI, 1.30-2.07) times more likely to have inadequate access to psychiatrists and 2.59 (95% CI, 1.82-3.69) times more likely to have no access to psychiatrists, compared with reference communities (average income without high income inequality); low-income communities without high income inequality were 1.37 (95% CI, 1.05-1.78) times more likely to have inadequate access to psychiatrists and 1.93 (95% CI, 1.28-2.89) times more likely to have no access to psychiatrists. Rural communities were 6.65 (95% CI, 5.09-8.69) times more likely to have inadequate access to psychiatrists than urban communities. Conclusions and Relevance In this cohort study of US communities, 35% of TRICARE beneficiaries lived in communities with inadequate access to psychiatrists. Psychiatric capacity was structurally inequitable along 2 separate dimensions: the income gradient and rurality. Developing targeted strategies for these shortage areas could alleviate disparities.
Opportunities for Clinicians and Health Systems to Address Disparities in US Drug Overdose Deaths by Race and Ethnicity—Reply
Authors: Mbabazi Kariisa, Puja Seth, Christopher M. Jones
Journal: JAMA (2023)

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Development of a Model to Estimate the Optimal Number of Oocytes to Attempt to Fertilize During Assisted Reproductive Technology Treatment
Authors: Katharine F. B. Correia, Stacey A. Missmer, Rachel Weinerman, Elizabeth S. Ginsburg, Brooke V. Rossi
Journal: JAMA Network Open (2023)

Importance Surplus cryopreserved embryos pose a challenge for in vitro fertilization patients and clinics; with Roe v. Wade overturned, some states may deem the discarding of surplus embryos illegal, radically changing in vitro fertilization practice. An evidence-based tool would help limit surplus embryo creation. Objective To develop a prediction tool for determining how many oocytes should be exposed to sperm to create embryos to conserve the chance of live birth while minimizing surplus embryos. Design, Setting, and Participants This diagnostic study used data from member clinics of the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System between 2014 to 2019. A total of 410 719 oocyte retrievals and 460 577 embryo transfer cycles from 311 237 patients aged 18 to 45 years old who initiated their first oocyte stimulation cycle between January 1, 2014, and December 31, 2019, were included. Data were analyzed from February to June 2022. Exposures Female patient age, anti-mullerian hormone level, diminished ovarian reserve diagnosis, number of oocytes retrieved, and the state where the clinic is located were included in the final models. Main Outcomes and Measures The algorithm was based on 3 models with outcomes: (1) day of transfer; (2) proportion of retrieved oocytes that become usable blastocysts; and (3) number of blastocysts needed for transfer for 1 live birth to occur. Results The median (IQR) age at stimulation cycle start was 35 (29-32) years and the median (IQR) number of oocytes retrieved was 10 (6-17). The likelihood of recommending that all oocytes be exposed to sperm increased with age; less than 20.0% of retrievals among patients younger than 32 years and more than 99.0% of retrievals among patients older than 42 years received recommendations that all oocytes be exposed to sperm. Among cycles recommended to expose fewer than all oocytes, the median (IQR) numbers recommended for 1 live birth were 7 oocytes (7-8) for patients aged less than 32 years, 8 (7-8) for patients aged 32 to 34 years, and 9 (9-11) for patients aged 35 to 37 years. Conclusions and Relevance In this diagnostic study of in vitro fertilization cycles, a prediction tool was developed to aid clinicians in determining the optimal number of oocytes to expose to sperm, reducing the number of unused embryos created and immediately addressing current patient and clinician concerns.
Scarlett McNally: The UK cannot afford for the NHS to fail
Authors: Scarlett McNally
Journal: BMJ (2023)

The NHS is facing a crisis: people are waiting hours in emergency departments, waiting in queuing ambulances, or dying on trolleys; staff morale is at an all time low.Yet underpinning the inhumanity is a crisis for the UK economy.The UK cannot afford for the NHS to fail.Having a healthy workforce is key to maintaining a prosperous economy.
Clinical practice recommendations for primary hyperoxaluria: an expert consensus statement from ERKNet and OxalEurope
Authors: Jaap W. Groothoff, Ella Metry, Lisa Deesker, Sander Garrelfs, Cecile Acquaviva, Reham Almardini, Bodo B. Beck, Olivia Boyer, Rimante Cerkauskiene, Pietro Manuel Ferraro, Luitzen A. Groen, Asheeta Gupta, Bertrand Knebelmann, Giorgia Mandrile, Shabbir S. Moochhala, Agnieszka Prytula, Jovana Putnik, Gill Rumsby, Neveen A. Soliman, Bhaskar Somani, Justine Bacchetta
Journal: Nature Reviews Nephrology (2023)
Meet the First Authors
Journal: Circulation Research (2023)

in 2010 and joined UAB, chasing his dreams of becoming a successful scientist.His research focuses on deciphering the molecular signaling linked with disease progression and its clinical manifestation so that an efficient interventional approach can be achieved.The primary area of his research is diabetes and its microvascular complications in the retina and heart.He is interested in exploring key mechanism(s), initiated by disturbed gut axis, which result in aberrant angiogenesis in retina and development of retinopathy and perivascular and interstitial cardiac fibrosis in diabetes.Outside the lab, he likes to spend time with his family and participate in indoor and outdoor activities.He can be found on Twitter @ramprasadUAB.
US and EU Free Trade Agreements and implementation of policies to control tobacco, alcohol, and unhealthy food and drinks: A quasi-experimental analysis
Authors: Pepita Barlow, Luke N. Allen
Journal: PLoS Medicine (2023)

Identifying and tackling the factors that undermine regulation of unhealthy commodities is an essential component of effective noncommunicable disease (NCD) prevention. Unhealthy commodity producers may use rules in US and EU Free Trade Agreements (FTAs) to challenge policies targeting their products. We aimed to test whether there was a statistical relationship between US and EU FTA participation and reduced implementation of WHO-recommended policies.We performed a statistical analysis assessing the probability of at least partially implementing 10 tobacco, alcohol, and unhealthy food and drink policies in 127 countries in 2014, 2016, and 2019. We assessed differences in implementation of these policies in countries with and without US/EU FTAs. We used matching to conduct 48 covariate-adjusted quasi-experimental comparisons across 27 matched US/EU FTA members (87 country-years) and performed additional analyses and robustness checks to assess alternative explanations for our results. Out of our 48 tests, 19% (9/48) identified a statistically significant decrease in the predicted probability of at least partially implementing the unhealthy commodity policy in question, while 2% (1/48) showed an increase. However, there was marked heterogeneity across policies. At the level of individual policies, US FTA participation was associated with a 37% reduction (95%CI: -0.51 to -0.22) in the probability of fully implementing graphic tobacco warning policies, and a 53% reduction (95%CI: -0.63 to -0.43) in the probability of at least partially implementing smoke-free place policies. EU FTA participation was associated with a 28% reduction (95%CI: -0.45 to -0.10) in the probability of fully implementing graphic tobacco warning policies, and a 25% reduction (95%CI: -0.47 to -0.03) in the probability of fully implementing restrictions on child marketing of unhealthy food and drinks. There was a positive association with implementing fat limits and bans, but this was not robust. Associations with other outcomes were not significant. The main limitations included residual confounding, limited ability to discern precise mechanisms of influence, and potentially limited generalisability to other FTAs.US and EU FTA participation may reduce the probability of implementing WHO-recommended tobacco and child food marketing policies by between a quarter and a half-depending on the FTA and outcome in question. Governments negotiating or participating in US/EU FTAs may need to establish robust health protections and mitigation strategies to achieve their NCD mortality reduction targets.
Age-dependent Lamin changes induce cardiac dysfunction via dysregulation of cardiac transcriptional programs
Authors: Natalie J. Kirkland, Scott H. Skalak, Alexander J. Whitehead, James D. Hocker, Pranjali Beri, Geo Vogler, Bill Hum, Mingyi Wang, Edward G. Lakatta, Bing Ren, Rolf Bodmer, Adam J. Engler
Journal: Nature Aging (2022)
CD44‐Targeting Drug Delivery System of Exosomes Loading Forsythiaside A Combats Liver Fibrosis via Regulating NLRP3‐Mediated Pyroptosis
Authors: Lihong Gong, Honglin Zhou, Shenglin Zhang, Cheng Wang, Ke Fu, Cheng Ma, Yafang Zhang, Cheng Peng, Yunxia Li
Journal: Advanced Healthcare Materials (2023)

Abstract Liver fibrosis is a progressive pathological process induced by various stimuli and may progress to liver cirrhosis and cancer. Forsythiaside A (FA) is an active ingredient extracted from traditional Chinese medicine Forsythiae Fructus and has prominent hepatoprotective activities. However, the unsatisfactory pharmacokinetic properties restrict its clinical application. In this study, the nanocarrier of CD44‐specific ligand Hyaluronic acid (HA)‐modified milk‐derived exosomes (mExo) encapsulated with FA (HA‐mExo‐FA) is developed. As a result, HA modification could deliver drug‐loaded exosomes to the target cells and form a specific ligand‐receptor interaction with CD44, thus improving the anti‐liver fibrosis effect of FA. In vitro findings indicate that HA‐mExo‐FA could inhibit TGF‐ β 1‐induced LX2 cell proliferation, reduce α ‐SMA and collagen gene and protein levels, and promote the apoptosis of activated LX2 cells. In vivo results demonstrate that HA‐mExo‐FA could improve liver morphology and function changes in zebrafish larvae. The anti‐liver fibrosis mechanism of HA‐mExo‐FA may be attributed to the inhibition of NLRP3‐mediated pyroptosis. In addition, the effect of HA‐mExo‐FA on TAA‐induced increase in NLRP3 production is attenuated by NLRP3 inhibitor MCC950. Collectively, this study demonstrates the promising application of HA‐mExo‐FA in drug delivery with high specificity and provides a powerful and novel delivery platform for liver fibrosis therapy.
Centralization of Initial Care and Improved Survival of Poor Patients With Breast Cancer
Authors: Ann B. Nattinger, Nina A. Bickell, Maria J. Schymura, Purushottam Laud, Emily L. McGinley, Nicole Fergestrom, Liliana E. Pezzin
Journal: Journal of Clinical Oncology (2023)

PURPOSE Poor women with breast cancer have worse survival than others, and are more likely to undergo surgery in low-volume facilities. We leveraged a natural experiment to study the effectiveness of a policy intervention undertaken by New York (NY) state in 2009 that precluded payment for breast cancer surgery for NY Medicaid beneficiaries treated in facilities performing fewer than 30 breast cancer surgeries annually. METHODS We identified 37,822 women with stage I-III breast cancer during 2004-2008 or 2010-2013 and linked them to NY hospital discharge data. A multivariable difference-in-differences approach compared mortality of Medicaid insured patients with that of commercially or otherwise insured patients unaffected by the policy. RESULTS Women treated during the postpolicy years had slightly lower 5-year overall mortality than those treated prepolicy; the survival gain was significantly larger for Medicaid patients ( P = .018). Women enrolled in Medicaid had a greater reduction than others in breast cancer–specific mortality ( P = .005), but no greater reduction in other causes of death ( P = .50). Adjusted breast cancer mortality among women covered by Medicaid declined from 6.6% to 4.5% postpolicy, while breast cancer mortality among other women fell from 3.9% to 3.8%. A similar effect was not observed among New Jersey Medicaid patients with breast cancer treated during the same years. CONCLUSION A statewide centralization policy discouraging initial care for breast cancer in low-volume facilities was associated with better survival for the Medicaid population targeted. Given these impressive results and those from prior research, other policymakers should consider adopting comparable policies to improve breast cancer outcomes. [Media: see text]
“Cluster Bomb” Based Bismuth Nano‐in‐Micro Spheres Formed Dry Powder Inhalation for Thermo‐Radio Sensitization Effects of Lung Metastatic Breast Cancer
Authors: Qiyue Wang, Ji Liu, Daquan Chen, Si Miao, Jing Wen, Chang Liu, Shushu Xue, Yang Liu, Qingjie Zhang, Yan Shen
Journal: Advanced Healthcare Materials (2023)

Abstract Lung metastatic breast cancer (LMBC) is mainly diagnosed through CT imaging and radiotherapy could be the most common method in the clinic to inhibit tumor proliferation. While the sensitivity of radiotherapy is always limited due to the hypoxic tumor microenvironment and high doses of irradiation easily induce systemic cytotoxicity. Metal‐based materials applied as radiosensitizers have been widely investigated to improve efficiency and reduce the doses of irradiation. Herein, it is aimed to overcome these problems by designing biodegradable lipid‐camouflaged bismuth‐based nanoflowers (DP‐BNFs) as both a photo‐thermo‐radiosensitizer to develop a novel photothermal therapy (PTT) and radiotherapy combination strategy for LMBC treatment. To achieve effective lung deposition, “Cluster Bomb” structure‐based DP‐BNFs nano‐in‐micro dry powder inhalation (DP‐BNF@Lat‐MPs) are formulated through spray‐dried technology. The DP‐BNFs “cluster” in the microsphere to improve their tumor‐targeted lung deposition with a high fine particle fraction followed by burst releasing of DP‐BNFs for targeting delivery and LMBC therapy. The DP‐BNF@Lat‐MPs exhibit excellent photothermal conversion efficiency, radiotherapy enhancement, and CT imaging ability in vitro, which synergistically inhibit cell proliferation and metastasis. In vitro and in vivo data prove that combining PTT and radiotherapy with DP‐BNF@Lat‐MPs as a thermo‐radio dual‐sensitizer significantly enhances LMBC tumor metastasis inhibition with good biocompatibility and low toxicity.
Personalized Bacteria Loaded with Autoantigens for the Enhancement of Tumor Immunotherapy
Authors: Chenghu Wu, Wenjuan He, Yue Chen, Jie Cai, Fanjun Zeng, Zidong Lu, Jilong Wang
Journal: Advanced Healthcare Materials (2023)

Abstract Currently, tumor immunotherapy is becoming a new revolution in tumor treatment. Generated from tumor cell lysate (TCL) or irradiated tumor cells, the whole tumor antigen‐based vaccines have the possibility to enhance antitumor immune response without survival from immune surveillance in personalized immunotherapy. Here, polydopamine nanoparticles (PDA NPs) after self‐polymerization are covalently coated with TCL to form PDA@CL. Engineered Salmonella (EnS) wrapped with PDA@CL (EnS@PDA@CL) is targeted the localization of the tumor site by intravenous administration. EnS@PDA@CL delivered autologous antigen‐containing nanoparticles to tumor hypoxia regions through blood circulation. The PDA@CL particles promote the maturation of dendritic cells (DCs), thus eliciting the infiltration of whole tumor antigens specific cytotoxic T lymphocytes, significantly triggering antitumor immunity. The tumor regression in the Panc02 mice confirms the therapeutic potential of EnS@PDA@CL in clinical personalized immunotherapy.
T lymphocytes induce human cancer cells derived from solid malignant tumors to secrete galectin-9 which facilitates immunosuppression in cooperation with other immune checkpoint proteins
Authors: Stephanie Schlichtner, Inna M Yasinska, Gurprit S Lall, Steffen M Berger, Sabrina Ruggiero, Dietmar Cholewa, Nijas Aliu, Bernhard F Gibbs, Elizaveta Fasler-Kan, Vadim V Sumbayev
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Galectin-9 is a member of the family of lectin proteins and crucially regulates human immune responses, particularly because of its ability to suppress the anticancer activities of T lymphocytes and natural killer cells. Recent evidence demonstrated that galectin-9 is highly expressed in a wide range of human malignancies including the most aggressive tumors, such as high-grade glioblastomas and pancreatic ductal adenocarcinomas, as well as common malignancies such as breast, lung and colorectal cancers. However, solid tumor cells at rest are known to secrete either very low amounts of galectin-9 or, in most of the cases, do not secrete it at all. Our aims were to elucidate whether T cells can induce galectin-9 secretion in human cancer cells derived from solid malignant tumors and whether this soluble form displays higher systemic immunosuppressive activity compared with the cell surface-based protein. Methods A wide range of human cancer cell lines derived from solid tumours, keratinocytes and primary embryonic cells were employed, together with helper and cytotoxic T cell lines and human as well as mouse primary T cells. Western blot analysis, ELISA, quantitative reverse transcriptase-PCR, on-cell Western and other measurement techniques were used to conduct the study. Results were validated using in vivo mouse model. Results We discovered that T lymphocytes induce galectin-9 secretion in various types of human cancer cells derived from solid malignant tumors. This was demonstrated to occur via two differential mechanisms: first by translocation of galectin-9 onto the cell surface followed by its proteolytic shedding and second due to autophagy followed by lysosomal secretion. For both mechanisms a protein carrier/trafficker was required, since galectin-9 lacks a secretion sequence. Secreted galectin-9 pre-opsonised T cells and, following interaction with other immune checkpoint proteins, their activity was completely attenuated. As an example, we studied the cooperation of galectin-9 and V-domain Ig-containing suppressor of T cell activation (VISTA) proteins in human cancer cells. Conclusion Our results underline a crucial role of galectin-9 in anticancer immune evasion. As such, galectin-9 and regulatory pathways controlling its production should be considered as key targets for immunotherapy in a large number of cancers.
Real-world use of blinatumomab in adult patients with B-cell acute lymphoblastic leukemia in clinical practice: results from the NEUF study
Authors: Nicolas Boissel, Sabina Chiaretti, Cristina Papayannidis, Josep-Maria Ribera, Renato Bassan, Andrey N. Sokolov, Naufil Alam, Alessandra Brescianini, Isabella Pezzani, Georg Kreuzbauer, Gerhard Zugmaier, Robin Foà, Alessandro Rambaldi
Journal: Blood Cancer Journal (2023)

Abstract This retrospective observational study (NEUF) included adult patients with B-cell acute lymphoblastic leukemia (B-cell ALL) who had received blinatumomab for the treatment of minimal residual disease-positive (MRD+) or relapsed/refractory (R/R) B-cell ALL via an expanded access program (EAP). Patients were eligible if blinatumomab was initiated via the EAP between January 2014 and June 2017. Patients were followed from blinatumomab initiation until death, entry into a clinical trial, the end of follow-up, or the end of the study period (December 31, 2017), whichever occurred first. Of the 249 adult patients included, 109 were MRD+ (83 Philadelphia chromosome-negative [Ph−] and 26 Philadelphia chromosome-positive [Ph+]) and 140 had a diagnosis of R/R B-cell ALL (106 Ph− and 34 Ph+). In the MRD+ group, within the first cycle of blinatumomab treatment, 93% ( n = 49/53) of Ph− and 64% ( n = 7/11) of Ph+ patients with evaluable MRD achieved an MRD response (MRD &lt;0.01%). Median overall survival (OS) was not reached over a median follow-up time of 18.5 months (Ph−, 18.8 [range: 5.1–34.8] months; Ph+, 16.5 [range: 1.8–31.6] months). In the R/R group, within two cycles of blinatumomab, 51% of Ph− and 41% of Ph+ patients achieved complete hematologic remission (CR/CRh/CRi), and 83% of Ph− and 67% of Ph+ MRD-evaluable patients in CR/CRh/CRi achieved an MRD response. Median (95% confidence interval) OS was 12.2 (7.3–24.2) months in the R/R Ph− subgroup and 16.3 (5.3–not estimated) months in the R/R Ph+ subgroup. This large, real-world data set of adults with B-cell ALL treated with blinatumomab confirms efficacy outcomes from published studies.
Pre-lymphodepletion &amp; infusion endothelial activation and stress index as predictors of clinical outcomes in CAR-T therapy for B-cell lymphoma
Authors: Aldo A. Acosta-Medina, Isla McKerrow Johnson, Radhika Bansal, Matthew Hathcock, Saad J. Kenderian, Urshila Durani, Arushi Khurana, Yucai Wang, Jonas Paludo, Jose C. Villasboas, N. Nora Bennani, Patrick B. Johnston, Stephen M. Ansell, Yi Lin, Hassan B. Alkhateeb
Journal: Blood Cancer Journal (2023)